title: Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer.
abstract: OBJECTIVE
  68Ga-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-F(ab')2-trastuzumab [68Ga-DOTA-F(ab')2-trastuzumab] has been developed at our institution as a positron imaging reagent for assessing human epidermal growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial studies on animals demonstrated promising results in the monitoring of treatment response to heat shock protein 90-targeted drugs that inhibit the client protein HER2. We report here our initial clinical experience in the assessment of the toxicity, pharmacokinetics, biodistribution, and dosimetry profile of 68Ga-DOTA-F(ab')2-trastuzumab with PET/computed tomography using a mean of 236 MBq/5 mg administered intravenously.
  
  
  METHODS
  A group of 16 women with breast cancer were enrolled in this study. The one patient who did not receive 68Ga-DOTA-F(ab')2-trastuzumab was excluded from analysis. Both HER2-negative (n=7) and HER2-positive (n=8) cases were studied. Among the latter, seven had undergone trastuzumab treatment previously and one had not.
  
  
  RESULTS
  It was determined that 68Ga-DOTA-F(ab')2-trastuzumab was well tolerated, with a T½ of ≈ 3.6 ± 0.9 h; the critical organ was the kidney, with a mean dose of 0.383 cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive disease.
  
  
  CONCLUSIONS
  The reagent is safe, and assessments through additional studies in a better-defined group of patients, using larger administered masses of antibodies, with a better immunoreactive fraction are needed.
authors.affiliation: aDepartment of Radiology, Molecular Imaging and Therapy Service bDepartment of Medicine, Breast Cancer Medicine Service cHuman Oncology and Pathogenesis Program dDepartment of Medical Physics eRadiochemistry and Molecular Imaging Probes Core Facility, Memorial Sloan-Kettering Cancer Center Departments of fRadiology gMedicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Beylergil
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Morris
authors.forename: Peter M
authors.initials: PM
authors.lastname: Smith-Jones
authors.forename: Shanu
authors.initials: S
authors.lastname: Modi
authors.forename: David
authors.initials: D
authors.lastname: Solit
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Donoghue
authors.forename: Serge K
authors.initials: SK
authors.lastname: Lyashchenko
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Akhurst
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011874:Radiometry; D012449:Safety; D014057:Tomography, X-Ray Computed; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D000068878:Trastuzumab